Delayed adverse effects of neonatal exposure to polymeric nanoparticle poly(ethylene glycol)-block-polylactide methyl ether on hypothalamic-pituitary-ovarian axis development and function in Wistar rats

Reprod Toxicol. 2015 Nov:57:165-75. doi: 10.1016/j.reprotox.2015.07.072. Epub 2015 Jul 17.

Abstract

We studied delayed effects of neonatal exposure to polymeric nanoparticle poly(ethylene glycol)-block-polylactide methyl ether (PEG-b-PLA) on the endpoints related to pubertal development and reproductive function in female Wistar rats from postnatal day 4 (PND4) to PND 176. Female pups were injected intraperitoneally, daily, from PND4 to PND7 with PEG-b-PLA (20 or 40mg/kg b.w.). Both doses of PEG-b-PLA accelerated the onset of vaginal opening compared with the control group. In the low-dose PEG-b-PLA-treated group, a significantly reduced number of regular estrous cycles, increased pituitary weight due to hyperemia, vascular dilatation and congestion, altered course of hypothalamic gonadotropin-releasing hormone-stimulated luteinizing hormone secretion, and increased progesterone serum levels were observed. The obtained data indicate that neonatal exposure to PEG-b-PLA might affect the development and function of hypothalamic-pituitary-ovarian axis (HPO), and thereby alter functions of the reproductive system in adult female rats. Our study indicates a possible neuroendocrine disrupting effect of PEG-b-PLA nanoparticles.

Keywords: Endocrine disruptors; Estrous cycle; Nanotoxicology; PEG-b-PLA; Pituitary; Polymeric nanoparticles; Progesterone; Reproductive toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / pharmacology
  • Hypothalamo-Hypophyseal System / drug effects
  • Lactates / toxicity*
  • Luteinizing Hormone / blood
  • Male
  • Nanoparticles / toxicity*
  • Organ Size / drug effects
  • Ovary
  • Pituitary Gland / drug effects*
  • Pituitary Gland / growth & development
  • Pituitary Gland / metabolism
  • Pituitary Gland / pathology
  • Pituitary-Adrenal System / drug effects
  • Polyethylene Glycols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Progesterone / blood
  • Rats, Wistar

Substances

  • Lactates
  • poly(lactic acid-ethylene glycol)
  • Gonadotropin-Releasing Hormone
  • Polyethylene Glycols
  • Progesterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone